gov Paper 60
571-272-7822 Entered: February 15, 2018
v.
Case IPR2016-01542
Patent 8,952,138 B2
____________
INTRODUCTION
Petitioner, Apotex, Inc. and Apotex Corp.1 (hereinafter jointly
“Petitioner”) filed a Petition requesting institution of an inter partes review
of claims 1–24 of U.S. Patent No. 8,952,138 B2 (“the ’138 patent”). Paper 2
(“Pet.”). Patent Owner, Amgen Inc. and Amgen Manufacturing Corp.
(herein collectively “Patent Owner”) filed a Preliminary Response. Paper 9
(“Prelim. Resp.”). We instituted trial to determine whether the challenged
claims were patentable. Paper 10. Patent Owner filed a response. Papers
14/15. 2 (“Resp.”). Petitioner filed a reply. Papers 25/26. (“Reply”). Oral
Argument was heard on December 13, 2017, and a transcript of the record
has been made of record. Paper 59. Multiple unopposed motions to seal and
multiple opposed motions to exclude and submit supplemental information
are pending in this proceeding. See, e.g. Papers 16, 27, 33, 31, 37, 40,
43/44, 47, and 50.
For the reasons that follow, and based upon the totality of evidence in
the record, we determine that Petitioner has carried its burden of persuasion
that claims 1–17 and 19–24 of this patent are unpatentable. We also
1
Apotex Pharmaceuticals Holdings, Inc., Apotex Holdings, Inc., and
ApoPharma USA, Inc., and Intas Pharmaceuticals Limited are said to be
additional real parties in interest. Pet. 2.
2
As we grant certain of the motions to seal, we use this designation to
indicate the paper numbers of the unredacted and redacted (public) versions
of the same document where applicable.
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determine that Petitioner has not carried its burden of persuasion that claim
18 of this patent is unpatentable
A. Related Matters
Petitioner asserts that the ’138 patent is the subject matter of district
court litigation in the United States District Court for the Southern District
of Florida.3 Pet. 2. Petitioner further cites to related administrative matters,
including nonprovisional patent applications, as related.4 Pet. 2. Patent
Owner points out that the district court litigation concerning Petitioner’s
invalidity defenses was resolved in its favor. Prelim. Resp. 4, Ex. 2004, 4–5.
(“The Court finds that Apotex failed to meet its burden of establishing by
clear and convincing evidence that the ’138 patent is invalid for
obviousness. The Court thus finds that each of the asserted claims 1-3, 6, 7,
13, 15-17, 22-23 of the ’138 Patent is not invalid for obviousness under 35
U.S.C. § 103.”) Id. at 5. While informative, the standards are different
between the two proceedings, and the district court’s decision is not binding
upon this board.
3
Amgen Inc. et al. v. Apotex Inc. et al., No. 0:15-CV-61631-JIC/BSS (S.D.
Fla.).
4
U.S. Patent Application Serial Numbers 14/611,037 and 14/793,590.
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February 10, 2015, from an application that was filed June 21, 2010. Id.,
(22), (45). The ’138 patent describes that the expression of recombinant
proteins in the prior art prokaryotic systems is problematic in that the
expressed proteins have limited solubility precipitates called inclusion
bodies, which are improperly folded proteins. Id. at 1:18–33. According to
the specification of the ‘138 patent:
[V]arious methods have been developed for obtaining correctly
folded proteins from bacterial inclusion bodies. These methods
generally follow the procedure of expressing the protein, which
typically precipitates in inclusion bodies, lysing the cells,
collecting the inclusion bodies and then solubilizing the
inclusion bodies in a solubilization buffer comprising a
denaturant or surfactant and optionally a reductant, which
unfolds the proteins and disassembles the inclusion bodies into
individual protein chains with little to no structure.
Subsequently, the protein chains are diluted into or washed with
a refolding buffer that supports renaturation to a biologically
active form.
Id. at 1:34–47.
of 2.0 g/L and higher, with any meaningful degree of efficiency on a small
scale, and notably not on an industrial scale.” Id. at 2:17–21.
Id. 2:52–61.
C. Illustrative Claim
All of the patent claims are challenged. In particular, they are claims
1–24. Pet. 3. Of these challenged claims, claim 1 is independent. Claims 2–
24 depend, either directly or indirectly, from claim 1.
Claim 1 is illustrative, and reproduced below:
1. A method of refolding a protein expressed in a non-
mammalian expression system and present in a volume at a
concentration of 2.0 g/L or greater comprising:
(a) contacting the protein with a refold buffer comprising
a redox component comprising a final thiol-pair ratio having a
range of 0.001 to 100 and a redox buffer strength of 2 mM or
greater and one or more of:
(i) a denaturant;
(ii) an aggregation suppressor; and
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5
Referred to throughout the Petition as “Inclonals.” We use the first
author’s name, for consistency.
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II. ANALYSIS
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) any differences between the claimed subject matter and the prior art;
(3) the level of ordinary skill in the art; and (4) objective evidence of
nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
One seeking to establish obviousness based reference combination of
teachings also must articulate sufficient reasoning with rational
underpinnings to combine teachings. See KSR Int’l Co. v. Teleflex, Inc., 550
U.S. 398, 418 (2007).
A. The Person of Ordinary Skill In the Art at the Time of Invention
Petitioner proposes that the person of ordinary skill in the art to which
the ’138 Patent is directed “would have had at least a Bachelor’s degree (or
the equivalent) in Biochemistry or Chemical Engineering with several years’
experience in biochemical manufacturing, protein purification, and protein
refolding, or alternatively, an advanced degree (Masters or Ph.D.) in
Biochemistry or Chemical Engineering with emphasis in these same areas.”
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Pet. 18. “This person may also work in collaboration with other scientists
and/or clinicians who have experience in protein refolding or related
disciplines.” Pet. 18–19 Finally, Petitioner asserts that this person “would
have easily understood the prior art references referred to herein and would
have had the capacity to draw inferences from them.” Id.
Patent Owner asserts that a person of ordinary skill in the relevant art,
(the art of protein refolding in June of 2009, the priority date of the ’138
Patent) “would have had a Ph.D. degree in biochemistry, biochemical
engineering, molecular biology, or a related biological/chemical/engineering
discipline, or a master’s degree in such disciplines and several years of
industrial experience producing proteins in non-mammalian expression
systems.” Prelim. Resp. 18; Resp. 14.
These two descriptions are mostly consistent, but we adopt the
slightly higher level recited by Patent Owner, requiring a graduate level of
education and experience. Ex. 2001, ¶ 17. This is due to the sophistication
and complexity in the area of protein refolding. Ex. 2001, ¶ 16. A person of
ordinary skill in the art would have an advanced degree in biochemistry with
an engineering component and significant experience in protein production,
including refolding. Id. ¶ 17. This is also the level of ordinary skill in the
art reflected by the prior art of record. See Okajima v. Bourdeau, 261 F.3d
1350, 1355 (Fed. Cir. 2001); In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir.
1995); In re Oelrich, 579 F.2d 86, 91 (CCPA 1978).
B. Claim Construction
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their broadest reasonable construction in light of the
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protein
Petitioner argues that “protein” should not be construed as a “complex
protein.” Pet. 20.
The following passage of the Specification, which defines “protein”
gives us a clear definition:
As used herein, the terms “protein” and “polypeptide” are used
interchangeably and mean any chain of at least five naturally or
non-naturally occurring amino acids linked by peptide bonds.
Ex. 1001, 6:20-27, Resp. 18, fn. 4. This construction has changed from that
in the institution decision to reflect the claim language more accurately. See
Response 18, n. 4.
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2[oxidant] + [reductant].
Ex. 1001, 6:29-38. Resp. 20–21, fn. 5. This construction also has changed
from that in the institution decision to reflect the claim language more
accurately. See Response 18, n. 5.
refold mixture
Ex. 1001, 4:23–27 (emphases added). There was discussion at the oral
argument as to which of these descriptions was the broadest reasonable
definition. Paper 59, 13–14 and 31–35. Dr. Robinson testifies that the
single use of the broader description is correct. Ex. 1056, ¶¶ 5–7. Patent
Owner urges otherwise. Resp. 17, citing Ex. 2020 ¶ 9.
We agree with Patent Owner that the evidence of record in the
specification is more persuasive. The specification has set forth a definition
multiple times, and that it is the definition is evidenced by the use of “i.e.”
(id est, or “that is”). In contrast, “e.g.” (exempli gratia, or “for example”)
does not indicate a definition. We also observe that the use of the “e.g.”
appears intended to exemplify both the simple protein and complex protein
antecedents expansively defining how the method may be applied. Ex.
1001, 4:23–27.
October 11, 2007, and entitled “Method for Refolding a Protein.” Ex. 1003
(10), (21), (22), (43), (54). Based on its publication date, Schlegl is prior art.
Schlegl describes methods for protein refolding, including the
refolding and production of recombinant proteins. Ex.1003 at Abstract, ¶ 4.
Schlegl utilizes a dilution method of protein refolding that results in a
protein concentration up to 10 mg/ml. Id. ¶¶ 4–8, 16.
Schlegl delineates a continuous process that optimizes flow rate by
keeping the concentration of unfolded proteins low and adding the protein
solution at a flow rate that gives the unfolded protein time to properly fold.
Id. ¶¶ 33–61. Before mixing, Schlegl starts with a high concentration of
unfolded protein. Id. at ¶ 40.
Schlegl further describes a refolding buffer with a redox system
having a defined thiol-pair ratio and redox buffer strength. Id. ¶¶ 36, 41, 75.
The refolding buffer also contains a denaturant, an aggregation suppressor,
and/or a protein stabilizer. Id. ¶¶36, 41, 74-75.
(2) Hevehan (Ex. 1004)
Hevehan is prior art to the ’138 Patent. Ex. 1004
Hevehan describes refolding proteins from inclusion bodies at high
concentrations. Using multiple dilution profiles, Hevehan created an
experimental matrix to investigate different effects and the relationship
between variables to optimize yields at higher concentrations, arriving at
concentrations higher than 2 g/L. Id. at 5–6, Figure 4.
By varying the concentrations of reducing agent dithiothreitol
(“DTT”) and oxidizing agent oxidized glutathionone (“GSSG”) in the redox
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its biologically active form.” Ex. 1056 ¶24 (citing Ex. 1003, 13). She
testifies that it is her view that “the method of claim 9 of Schlegl cannot be
practiced without redox chemistry for proteins with disulfide bonds in the
native state. If one is working with a protein with disulfide bonds, it is
unlikely that one can obtain a biologically active form without the use of
redox components.” Ex. 1056, ¶ 24.
Dr. Willson testified in his second declaration that Schlegl and
Hevehan, alone or in combination, do not teach elements of claim 1; a
person of ordinary skill in the art would not combine the references; and the
art does not render the claims obvious. Ex. 2020, passim.
Dr. Robinson was cross-examined on May 8, 2017, in Washington,
DC. A transcript of that deposition testimony is in the record as Exhibit
2019. Dr. Willson likewise was cross-examined, on August 9, 2017, in New
York, NY. A transcript of that deposition testimony is in the record as
Exhibit 1055. Subsequent to her second declaration, Dr. Robinson was
again cross-examined on September 26, 2017, and a transcript of that cross-
examination is in the record as Exhibit 2059. We have carefully reviewed
the testimony provided by both witnesses.
We credit the testimony of Dr. Robinson on this point over that of Dr.
Willson. We are especially persuaded by the fact that simply diluting the
protein concentration will not necessarily result in refolding. Reply, 5. Dr.
Robinson also makes a compelling point that using a dilution technique to
contact a protein-containing volume with a refold buffer does not exclude
the use of redox agents. Ex. 1056, ¶ 15.
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She further testifies that Schlegl teaches the use of redox chemistry
and a customized refold buffer. Id. at
¶ 17, citing Ex. 1003, ¶ 36. Paragraph 36 is reproduced below:
The refolding buffer used for a given protein of interest is
customized to the refolding requirements/kinetics of that protein.
Refolding buffers are known in the art and commercially available;
typical buffer components are guadinium chloride, dithiothreitol
(DTT) and optionally a redox system (e.g. reduced glutathione
GSH/oxidized glutathione GSSG), EDTA, detergents, salts, and
refolding additives like L-arginine.
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Ex. 1004, 5.
We read this paragraph, contained in a section headed Thiol
Concentration Dependence on Renaturation, and sandwiched between a
discussion of the prior art thiol concentrations in the renaturation buffer and
empirical studies of different ranges as suggesting quite the opposite – as
teaching that one of ordinary skill in the art could find workable ranges by
routine experimentation.
Patent Owner also asserts that host-cell contaminants would lead one
of ordinary skill in the art not to have an expectation of success as model
proteins are not predictive of or applicable to recombinant proteins
expressed in mammalian expression systems. Resp. 2–3 and 27–32. The
evidence relied upon for this proposition is a publication originating from
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the same laboratory that the authors of Hevehan occupied. Id. (citing Ex.
2033).
Again, the weakness in this position is that the authors of the relied
upon exhibit(i.e. Ex. 2033) came to no such conclusion themselves. Patent
Owner selectively relies upon a single example to state: “It decreased by
40% to 50%.” Resp. 30. While this again may be literally true, and Patent
Owner includes a chart referencing what appears to be the single worst
example in the reference, we reproduce the abstract of the reference below to
provide additional context:
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conditions Hevehan was using for its measurements. Reply, 10. Petitioner
also observes that Buswell’s theory has been discredited. Id. (citing Ex.
1056 ¶¶34-35, Ex. 1057, 91, 95).
We note that Ex. 1057 does expressly negate a principal conclusion of
Buswell:
Buswell and Middelberg (2003) reported that the presence of
native lysozyme significantly decreased the effective refolding yield.
This was because that native lysozyme was able to polymerize with
aggregates (Buswell and Middelberg, 2002). We checked this
possibility by adding pure native sGFPmut3.1 in our refolding buffer
before refolding.
In contrast to decrease in yields in the presence of native
lysozyme (Buswell and Middelberg, 2003), refolding yields remained
unaffected in the presence of pure native sGFPmut3.1 (Fig. 3).
Ex. 1057, 5.
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2
2
2
Ex. 1002, fn3.
Two is within the claimed ratio range of 0.001-100.
Dr. Robinson calculates the redox buffer strength as well:
Based on the ‘138 patent, the redox buffer strength (BS) is defined by
the equation, [R]BS=2oxidant + [reductant]. In this case,
[R]BS=2[cysteine]+[cysteine]=6.6
6
We observe that Dr. Robinson did not show all of her work; however, it is
readily apparent to us that RBS=2[2 mM]+2 mM = 4+2 = 6 mM.
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Resp. 15.
Patent Owner’s first argument is that neither Schlegl or Hevehan
describe the TPR and RBS equations. Id. at 22. According to Patent Owner,
Dr. Robinson utilized the equations from the ‘138 Patent which is hindsight.
Id. at 23.
While an interesting argument, we are not persuaded of its legal
correctness. The TPR and RBS equations define ratios and concentrations
of oxidant and reductant. In order to discern whether the claims are obvious,
we of necessity must determine whether the prior art ratios and
concentrations render the claimed range obvious. Petitioner is correct in
observing that “where the general conditions of a claim are disclosed in the
prior art, it is not inventive to discover the optimum or workable ranges by
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Response 33.
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refolding tank to allow complete refolding of the protein. Pet. 48 (citing Ex.
1003 ¶¶ 16, 60). Patent Owner does not significantly dispute this teaching.
(c) isolating the protein from the refold mixture.
Lastly, Petitioner asserts that Schlegl discloses isolation of the protein
from the refold mixture as a final step in the disclosed refold method,
including via dialysis, filtration, extraction, precipitation and
chromatography. Pet. 48 (citing Ex. 1003 ¶¶ 39, 65). Patent Owner does
not significantly dispute this teaching.
On consideration of the evidence presented at trial, including Patent
Owner’s evidence to the contrary, we find Petitioner to have met its burden
of proof. We conclude that claim 1 is unpatentable as obvious over Schlegl
and Hevehan.
Claim 2
Claim 2 depends from claim 1, and further recites that the final thiol-
pair ratio is selected from the group consisting of 0.05 to 50, 0.1 to 50, 0.25
to 50, 0.5 to 50, 0.75 to 40, 1.0 to 50 and 1.5 to 50, 2 to 50, 5 to 50, 10 to 50,
15 to 50, 20 to 50, 30 to 50 or 40 to 50. Ex. 1001, 17:60–18:2.
Petitioner asserts that Schlegl describes contacting the protein with a
refold buffer with a thiol-pair ratio of 2. Pet. 49 (citing Ex. 1003 at ¶ 75).
Hevehan is said to describe a thiol pair ratio of 0.3 to 9. Id. (citing Ex. 1004,
5). Patent Owner does not separately argue claim 2.
As the evidence shows that the final TPR in Schlegl and Hevehan fall
within several of the claimed ranges of claim 2, we are persuaded that
Petitioner has demonstrated that challenged claim 2 is unpatentable as
obvious over Schlegl and Hevehan.
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Claim 3
Claim 3 depends from claim 1 and further recites that the thiol-pair
buffer strength is selected from the group consisting of greater than or equal
to 2.25 mM, 2.5 mM, 2.75 mM, 3 mM, 5 mM, 7.5 mM, 10 mM and 15mM.
Ex. 1001, 18:3–6.
Petitioner asserts that the example in Schlegl describes a redox buffer
strength of 6 mM. Pet. 49 (citing Ex. 1003 ¶ 75). Hevehan is also said to
describe a redox buffer strength of 5 to 19 mM, with an optimum 10 to 16
mM. Id. (citing Ex. 1004, 5). Both disclosures are urged to fall within the
scope of claim 3. Patent Owner does not separately argue claim 3.
As the final RBS in Schlegl and Hevehan appear to fall within the
claimed range of claim 3, we are persuaded that Petitioner has demonstrated
that challenged claim 3 is unpatentable as obvious over Schlegl and
Hevehan.
Claims 4 and 5
Claim 4 depends from claim 1, and further recites that the protein is
present in the volume in a non-native limited solubility form. Ex. 1001,
18:7–8. Claim 5 depends from claim 4, and further recites that the form is
an inclusion body. Id. 18:9–10.
Petitioner asserts that Schlegl discloses that the protein is deposited in
the cells in a paracrystalline form, in so-called “inclusion bodies,” also
termed “refractile bodies.” Pet. 52–53 (citing Ex. 1003 ¶ 6). Hevehan is said
to describe that the “[a]ctive protein can be recovered by solubilization of
inclusion bodies followed by renaturation of the solubilized (unfolded)
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protein.” Id. (citing Ex. 1004, Abstract). Patent Owner does not separately
argue claims 4 or 5.
As the evidence of record establishes that the final inclusion bodies in
Schlegl and Hevehan fall within the non-native limited solubility form of
claim 4, and the inclusion body of claim 5, we are persuaded that Petitioner
has demonstrated that challenged claims 4 and 5 are unpatentable as obvious
over Schlegl and Hevehan.
Claim 6
Claim 6 depends from claim 1, and recites that the protein is present
in the volume in a soluble form. Ex. 1001, 18:11–12.
Petitioner asserts that Schlegl describes a method of refolding a
protein, where that protein before refolding is dissolved as a protein solution.
Pet. 53 (citing Ex. 1003 ¶¶ 16, 63). Patent Owner does not significantly
argue claim 6.
As the evidence of record establishes that the protein solution in
Schlegl falls within the soluble form of claim 6, we are persuaded that
Petitioner has demonstrated challenged claim 6 is unpatentable as obvious
over Schlegl and Hevehan.
Claims 7-11
Claim 7 depends from claim 1, and further recites that the protein is
recombinant. Ex. 1001, 18:13–14. Claim 8 depends from claim 1 and
further recites that the protein is an endogenous protein. Id. 18:15–16.
Claim 9 depends from claim 1, and further recites that the protein is an
antibody. Id. 18:17–18. Claim 10 depends from claim 1, and further recites
that the protein is a complex protein. Id. 18:19–20. Claim 11 depends from
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claim 1, and further recites that the protein is a multimeric protein. Id.
18:21–22.
Petitioner asserts, alternatively, that Schlegl discloses a method of
refolding the various proteins identified in claims 7-11, and that one of
ordinary skill in the art would immediately recognize that the methods of
Schlegl could be applied. Pet. 53–54. Petitioner points to Schlegl’s
description that the methods can be applied to “any protein, protein fragment
or peptide that requires refolding upon recombinant expression in order to
obtain such protein in its biologically active form” Id. (citing Ex. 1003 ¶ 31).
Petitioner observes that Schlegl describes the refolding of bovine α-
lactalbumin, a protein containing 123 amino acid residues and four disulfide
bonds, while Hevehan describes refolding hen egg white lysozyme having
129 amino acids and four disulfide bonds. Pet. 54 (citing Ex., 1003, 1004).
Dr. Robinson testifies that a person of skill in the art would
immediately recognize that the methods taught by Schlegl could be applied
to each of these types of proteins, and in particular multimeric proteins, such
as antibodies. Ex. 1002, ¶ 145 (citing Ex. 1006 at 281).
Patent Owner does not separately argue claims 7 and 8. Patent
Owner, however, provides contrary arguments for claims 9, 10, and 11.
Patent Owner urges that none of the refolded proteins of Schlegl and
Hevehan are complex proteins as recited in claim 10. Resp. 42–44. More
specifically, Patent Owner asserts that there is no empirical evidence that a
person of ordinary skill in the art would have had a reasonable expectation
of success of refolding complex proteins, antibodies, or multimeric proteins.
Resp. 43. Dr. Willson testifies that neither Schlegl nor Hevehan “teach or
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suggest” the proteins required by claims 9, 10, and 11. Ex. 2020, ¶ 94. Dr.
Willson concedes that Schlegl broadly states that its method can be used on
“any protein, protein fragment or peptide that requires refolding upon
recombinant expression in order to obtain such protein in its biologically
active form.” Ex. 1003, ¶ 31. However, he would require an experimental
showing to support this assertion, not the model protein example actually
conducted. Patent Owner also observes that refolding complex proteins can
be “extremely difficult” and “challenging.” Resp. 43.
We accept that refolding proteins is difficult and challenging.
However, the person of ordinary skill in the art is highly skilled. The Petition
asserts that one of ordinary skill in the art would immediately recognize that
the methods of Schlegl could be applied to those types of molecules, and Dr.
Robinson’s testimony supports the statement made in Schlegl. Ex. 1002, ¶
145.
Dr. Robinson relies in part on Ex. 1006, which is a publication from
“mAbs” journal in 2009.7 We also take into account her cross-examination
testimony in which she stated:
7
Patent Owner asserts that Ex. 1006 is not prior art to their claims. They
have provided the declaration testimony of Dr. Roger A. Hart (Ex. 2021),
and internal Amgen presentations (Ex. 2022 and Ex. 2024) which are
considered to be confidential and subject to protective order. Exhibits 2022
and 2024 discuss protein AMG 745 and Exhibits 2023 and 2025 indicate the
documents were created in 2009 and 2008 However, other than the code
names of the proteins, no real identification of the type of protein that
designation reflects is made in the contemporaneous documents. Dr. Hart
testifies that AMG 745 falls within the scope of, e.g., claims 1, 7, 10, 11,
and 12(Ex. 2021, ¶ 35) , identification would have been unnecessary on
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Claims 19–24
Claim 19 depends from claim 1, and recites that the isolation
comprises contacting the mixture with an affinity separation matrix. Ex.
1001, 18:48–49. Claim 20 depends from claim 19, and recites that the
affinity separation matrix is a Protein A resin. Ex. 1001, 18:50–51. Claim
21 depends from claim 19, and further recites that the affinity resin is a
mixed mode separation matrix. Ex. 1001, 18:52–53. Claim 22 depends from
claim 1, and further recites that “the isolating comprises contacting the
mixture with an ion exchange separation matrix.” Ex. 1001, 18:54–56.
Claim 23 depends from claim 1, and recites that “the isolating further
comprises a filtration step.” Ex. 1001, 18:57–58. Claim 24 depends from
claim 23, and further recites that “the filtration step comprises depth
filtration.” Ex. 1001, 18:58–59.
Petitioner asserts that Claims 19–24 are directed to particular isolation
methods, each of which were well known in the art at the time of the
invention. . Pet. 55–56 (citing Ex. 1002 at ¶ 149). Petitioner urges that these
standard methods and their usage are the result of routine optimization, and
thus are not patentably distinguishing claim elements. Id. Additionally,
Petitioner observes that Schlegl describes that protein is separated and
purified according to methods known in the art, including, but not limited to,
dialysis, filtration, extraction, precipitation and chromatography techniques.
Pet. 56 (citing Ex. 1003 ¶ 65). Patent Owner does not meaningfully
separately argue claims 19–24.
As Schlegl describes customary known isolation methods, which fall
within the methods recited by these claims, and Dr. Robinson has testified to
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must credibly establish that AMG 745 is a fusion protein. We are told, that
AMG 745 is an Fc protein conjugate. Resp. 52. We are pointed to a passage
in Ex. 2026:
Antimyostatin peptibody (AMG 745) is a novel antimyostatin
peptibody. Structurally, it is a fusion protein with a human Fc at the N
terminus and a myostatin-neutralizing bioactive peptide at the C
terminus.
Ex. 2026, 2.
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V. CONCLUSION
For the foregoing reasons, we determine that Petitioner has
demonstrated that challenged claims 1–17 and 19–24 are unpatentable
Petitioner, however, has not demonstrated that challenged claim 18 is
unpatentable.
V. ORDER
Accordingly, it is ORDERED that:
Claims 1-11, 13-17 and 19-24 under 35 U.S.C. § 103(a) are
unpatentable over Schlegl and Hevehan
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PETITIONER:
Teresa Stanek Rea
Deborah H. Yellin
Vincent J. Galluzzo
Michael Jacobs
Shannon Lentz
CROWELL & MORING LLP
TRea@Crowell.com
DYellin@Crowell.com
VGalluzzo@Crowell.com
mjacobs@crowell.com
slentz@crowell.com
PATENT OWNER:
Arlene L. Chow
HOGAN LOVELLS US
arlene.chow@hoganlovells.com
Catherine Nyarady
PAUL, WEISS, RIFKIND, WHARTON & GARRISON LLP
cnyarady@paulweiss.com
49